It is very impressive for us that many three dimensional structure of biological macromolecules in atomic resolution appears as a scientific paper by means of protein crystallography and multi-dimensional NMR. Such structure sometime reveals new feature of the molecule, and suggests novel functional mechanism. Then we will have new objective on the bio-molecule. Structure-based drug design is utilizing such macro-molecular structure for developing novel therapeutics. Anti-retroviral agents for AIDS as inhibitors of HIV protease are known as a successful project of such structure- based design, and many reviews have been written in various aspects. A report of combination therapy of HIV protease inhibitor with established AIDS drug like Zidovudine was so sensational due to its optimistic clinical results in mass communication. Many inhibitors, which were developed with high selectivity and nano- molar affinity to HIV protease, have been employed to clarity the relationship between bio-availability and its chemical structure and molecular basis of drug resistance and so on in view from pharmacology. Several anti-viral projects are going on to inhibit viral protease essential for maturation of target viral particle. 3C proteases of Hepatitis A virus and its family, Cytomegalovirus proteases, and Hepatitis C viral proteases were reported on their crystal structures in Nature or Cell mostly by pharmaceutical companies including a couple of venture business specialized in structure-based.

I believe in the tight connection of "the function" and "its structure" in life, then structural biology in atomic resolution is a versatile tool for industrial R & D due to just manipulatable hierarchy 'in sight'. The natural history and taxonomy of bio- macromolecules in shape may open the ecology and physiology in action to assist the further application. Structural approach needs many discipline and there are many immature technology to be developed and improved when R & D is pursued, I think. I also believe that these objectives will be only overcome by the expansion of basic theory like as non-bonding interaction in solution. The proper target also should be considered like the HIV protease inhibitor as a structure-based design target among the many approaches for AIDS therapeutics. It is yet to be mature that the transmembrane- receptors or channel molecules, however which have been major drug targets, are selected as structure-based target due to few structural information are available up to now. It is crucial for us to pick-up executable goal, and I hope that the idea exchange and further co-laboration of research including other scientific fields will be conducted to carry out long term objects regardless in Japan or overseas Healthy "collaboratlon and competition" in any scientific fields will help to establish structural biology including its application. TARA Sakabe's project based on utilizing advanced synchrotron radiation facility will expand, I hope, as one of cores on sharing and releasing nodes of versatile structural information, resulting in the open space for cooperation and collaboration as a research infrastructure at work.

(e-mail:miyano@isrl.jti.co.jp)